title: CAR regulates epithelial cell junction stability through control of E-cadherin trafficking.
abstract: CAR (Coxsackie and Adenovirus Receptor) is the primary docking receptor for typeB coxsackie viruses and subgroup C adenoviruses. CAR is a member of the JAM family of adhesion receptors and is located to both tight and adherens junctions between epithelial cells where it can assemble adhesive contacts through homodimerisation in trans. However, the role of CAR in controlling epithelial junction dynamics remains poorly understood. Here we demonstrate that levels of CAR in human epithelial cells play a key role in determining epithelial cell adhesion through control of E-cadherin stability at cell-cell junctions. Mechanistically, we show that CAR is phosphorylated within the C-terminus by PKCδ and that this in turn controls Src-dependent endocytosis of E-cadherin at cell junctions. This data demonstrates a novel role for CAR in regulating epithelial homeostasis.
authors.affiliation: 1] Division of Asthma, Allergy & Lung Biology, King's College London, 5th Floor Tower Wing, Guy's Hospital Campus, London, United Kingdom [2] Randall Division of Cell and Molecular Biophysics, King's College London, New Hunt's House, Guys Campus, London, United Kingdom.
authors.forename: Penny E
authors.initials: PE
authors.lastname: Morton
authors.forename: Alexander
authors.initials: A
authors.lastname: Hicks
authors.forename: Theodoros
authors.initials: T
authors.lastname: Nastos
authors.forename: George
authors.initials: G
authors.lastname: Santis
authors.forename: Maddy
authors.initials: M
authors.lastname: Parsons
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051745:Protein Kinase C-delta / Q000378:metabolism; D021381:Protein Transport; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D015820:Cadherins; D011991:Receptors, Virus; C085301:adenovirus receptor; D019061:src-Family Kinases; D051745:Protein Kinase C-delta